Increasing the Transport of Celecoxib over a Simulated Intestine Cell Membrane Model Using Mesoporous Magnesium Carbonate

In the current work, mesoporous magnesium carbonate (MMC) was used to suppress crystallization of the poorly soluble drug celecoxib (CXB). This resulted in both a higher dissolution rate and supersaturation of the substance in vitro as well as an increased transfer of CXB over a Caco-2 cell membrane mimicking the membrane in the small intestine. The CXB flux over the cell membrane showed a linear behavior over the explored time period. These results indicate that MMC may be helpful in increasing the bioavailability and obtaining a continuous release of CXB, and similar substances, in vivo. Neusilin US2 was used as a reference material and showed a more rapid initial release with subsequent crystallization of the incorporated CXB in the release media. The presented results form the foundation of future development of MMC as a potential carrier for poorly soluble drugs.

Non-Proteinaceous Complexes III and IV Mimicking Electron Transfer in the Mitochondrial Respiratory Chain

<div><div><div><p>Synthetic biology pursues the understanding of biological processes and their possible mimicry with artificial bioinspired materials. We explore the redox properties of magnetic iron oxide nanoparticles to mimic the redox activity of complexes III and IV towards cytochrome c. We demonstrate that these nanoparticles, incorporated as non-proteinaceous complexes III and IV in a mitochondrial cell membrane model, catalyze electron transfer similarly to natural complexes. The associated molecular mechanism was experimentally proven in solution and in a Langmuir- Blodgett film; the protein-nanoparticle interactions are governed mainly by electrostatic forces, followed by electron transfer between the iron sites of the nanoparticles and the heme group. This work presents the first experimental demonstration that inorganic nanostructured systems may behave as proteins in the cell membrane.</p></div></div></div>

Non-Proteinaceous Complexes III and IV Mimicking Electron Transfer in the Mitochondrial Respiratory Chain

<div><div><div><p>Synthetic biology pursues the understanding of biological processes and their possible mimicry with artificial bioinspired materials. We explore the redox properties of magnetic iron oxide nanoparticles to mimic the redox activity of complexes III and IV towards cytochrome c. We demonstrate that these nanoparticles, incorporated as non-proteinaceous complexes III and IV in a mitochondrial cell membrane model, catalyze electron transfer similarly to natural complexes. The associated molecular mechanism was experimentally proven in solution and in a Langmuir- Blodgett film; the protein-nanoparticle interactions are governed mainly by electrostatic forces, followed by electron transfer between the iron sites of the nanoparticles and the heme group. This work presents the first experimental demonstration that inorganic nanostructured systems may behave as proteins in the cell membrane.</p></div></div></div>

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

Epigallocatechin-3-gallate (EGCG) has the highest antioxidant activity compared to the others catechins of green tea. However, the beneficial effects are mainly limited by its poor membrane permeability. A derivatization strategy to increase the EGCG interaction with lipid membranes is considered as one feasible approach to expand its application in lipophilic media, in particular the cellular absorption. At this purpose the hydrophilic EGCG was modified by inserting an aliphatic C18 chain linked to the gallate ring by an ethereal bond, the structure determined by NMR (Nuclear Magnetic Resonance) and confirmed by Density Functional Theory (DFT) calculations. The in vitro antioxidant activity of the mono-alkylated EGCG (C18-EGCG) was studied by the DPPH and Thiobarbituric Acid Reactive Substances (TBARS) assays, and its ability to protect cells towards oxidative stress was evaluated in Adult Retinal Pigmented Epithelium (ARPE-19) cells. Molecular Dynamics (MD) simulation and liposomal/buffer partition were used to study the interaction of the modified and unmodified antioxidants with a cell membrane model: the combined experimental-in silico approach shed light on the higher affinity of C18-EGCG toward lipid bilayer. Although the DPPH assay stated that the functionalization decreases the EGCG activity against free radicals, from cellular experiments it resulted that the lipid moiety increases the antioxidant protection of the new lipophilic derivative.

Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline

This work focuses on the interaction of the novel and representative antituberculosis (anti-TB) drug bedaquiline (BDQ) with different membrane models of eukaryotic and prokaryotic cells. The effect of BDQ on eukaryotic cell membrane models was assessed using liposomes, namely, multilamellar vesicles (MLVs) made of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) and also a mixture of DMPC and cholesterol (CHOL) (8:2 molar ratio). To mimic the prokaryotic cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and 1,1′2,2′-tetra-oleoyl-cardiolipin (TOCL) were chosen. Powerful biophysical techniques were employed, including small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS), to understand the effect of BDQ on the nanostructure of the membrane models. The results showed that BDQ demonstrated a pronounced disordering effect in the bacterial cell membrane models, especially in the membrane model with cardiolipin (CL), while the human cell membrane model with large fractions of neutral phospholipids remained less affected. The membrane models and techniques provide detailed information about different aspects of the drug–membrane interaction, thus offering valuable information to better understand the effect of BDQ on their target membrane-associated enzyme as well as its side effects on the cardiovascular system.